Abstract

Potassium ion channel proteins regulate electrical signaling in nervous systems. W'hile the crystal structure of a typical K' channel such as Streptomyces fividans membrane protein KcSA has been solved, the gating mechanism and the location topology in the membrane bilayer are not yet fully understood. High resolution solid-state NMR offers a number of ways to study the process in the solid state. We suggest to use """"""""Ti as a probe for analyzing location and movements of ions inside the protein. """"""""TI NMR in solid state offers a number of advantages; high gyromagnetic ratio of """"""""'TI and its large chemical shift dispersion allow to observe local structure with high sensitivity and efficiency. Preliminary experiments on model systems have been successfully performed. Our goal is to conduct variable temperature experiments on KcSA ion channel in order to determine the number of ion-binding sites, their topology and the dynamics of the process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR000995-24
Application #
6118668
Study Section
Project Start
1999-05-15
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
24
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

Showing the most recent 10 out of 12 publications